Aspirin Statins Or Both For The Reduction Of Thrombin Generation In Diabetic People (RATIONAL)

This study has been completed.
Sponsor:
Information provided by:
Fundacion GESICA
ClinicalTrials.gov Identifier:
NCT00793754
First received: November 18, 2008
Last updated: October 25, 2011
Last verified: October 2011
  Purpose

Despite formal recommendations, evidence of efficacy of aspirin in individuals with diabetes is scant and controversial. While the efficacy of aspirin versus placebo in patients with diabetes is currently under investigation in big randomized controlled trials, the putative additive effects of aspirin and statins in this population remain to be investigated. Moreover there are no data examining the pathophysiologic means by which aspirin with or without statins affects thrombosis in diabetic patients.

The aim of this trial is to evaluate the efficacy of low-dose aspirin (100 mg/daily), statins, both or neither for the reduction of thrombin generation. These preventive strategies will be evaluated on the top of the other strategies aimed at optimizing the care of diabetic patients in terms of metabolic control and control of the other cardiovascular risk factors.


Condition Intervention Phase
Diabetes Mellitus
Drug: Aspirin
Drug: Atorvastatin
Drug: Aspirin + Atorvastatin
Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Single Blind (Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Aspirin Statins Or Both For The Reduction Of Thrombin Generation In Diabetic People

Resource links provided by NLM:


Further study details as provided by Fundacion GESICA:

Primary Outcome Measures:
  • Thrombin generation [ Time Frame: 8 weeks ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • C-reactive protein [ Time Frame: 8 weeks ] [ Designated as safety issue: No ]

Enrollment: 30
Study Start Date: March 2009
Study Completion Date: October 2011
Primary Completion Date: October 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
No Intervention: 1
Experimental: 2
Aspirin 100 mg / day
Drug: Aspirin
100 mg / day for 8 weeks
Experimental: 3
Atorvastatin 40 mg / day
Drug: Atorvastatin
40 mg / day for 8 weeks
Experimental: 4
Aspirin 100 mg / day + Atorvastatin 40 mg / day
Drug: Aspirin + Atorvastatin
Aspirin 100 mg / day + Atorvastatin 40 mg / day for 8 weeks

Detailed Description:

Despite the very high cardiovascular risk profile, evidence of efficacy of aspirin in individuals with diabetes is scant.

The meta-analysis on the efficacy of antiplatelet therapy involving a total of about 5,000 diabetic subjects indicates a non significant reduction in the risk of major cardiovascular events of 7%, compared with a reduction of 25% documented in secondary prevention studies.

Diabetes could represent a special case of aspirin resistance, although no specific studies have, to our knowledge, fully explored this hypothesis. The poor platelet responsiveness to aspirin has been recently proposed as a possible explanation of the failure of antiplatelet therapy to prevent cardiovascular events. The reduction in the aspirin activity in some patients is indicated by the failure in adequately suppressing thromboxane-A2 synthesis, as documented by the presence of high levels of its urinary metabolites.

The substantial lack of clear evidence is reflected by the low use of this drug in clinical practice; in fact, only 10% of diabetic patients are treated with aspirin for the prevention of cardiovascular events.

On the other hand, statins provide a similar efficacy for the prevention of major cardiovascular events in populations with and without diabetes.

It has been recently shown that platelet response to aspirin is linearly reduced with increasing cholesterol plasma levels. The presence of dyslipidemia, particularly common among diabetic patients, could thus be at least partially responsible for a lower efficacy of aspirin in this population. The concomitant use of statins could thus restore the normal platelet sensitivity to aspirin by reducing cholesterol levels

One additional reason to hypothesize a positive effect of statins in improving platelet response to aspirin is related to their anti-inflammatory properties

While the efficacy of aspirin versus placebo in patients with diabetes is currently under investigation, the additive effects of aspirin and statins in this population remain to be investigated. This aspect is of particular interest in the light of the existing debate regarding the need of multiple interventions to reduce total cardiovascular risk.

Given these premises, it is important to evaluate the effectiveness of aspirin use in primary prevention of cardiovascular events in association with statins therapy when included in a strategy of global risk control.

The RATIONAL Study will evaluate whether the combined use of aspirin (100 mg d) and statins (Atorvastatin 40 mg daily) is superior to the use of these single agents for the reduction of thrombin generation in patients with diabetes and without previous cardiovascular events.

  Eligibility

Ages Eligible for Study:   50 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Diabetes mellitus treated with insulin or orl agents
  • At least 50 years old

Exclusion Criteria:

  • Previous cardiovascular events
  • current or past (within last 30 days) treatment with aspirin
  • current or past (within last 180 days) treatment with statins
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00793754

Locations
Argentina
Centro de Educación Médica e Investigaciones Clínicas (CEMIC)
Buenos Aires, Argentina
Sponsors and Collaborators
Fundacion GESICA
Investigators
Principal Investigator: Alejandro Macchia, MD Fundacion GESICA
Principal Investigator: Hernan Doval, MD Fundacion GESICA
Principal Investigator: Juan J Fuselli, MD Centro de Educación Medica e Investigaciones Clínicas Norberto Quirno
Principal Investigator: Pablo D Comignani, MD Hospital Aleman
  More Information

No publications provided by Fundacion GESICA

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Alejandro Macchia, Fundacion GESICA
ClinicalTrials.gov Identifier: NCT00793754     History of Changes
Other Study ID Numbers: 002
Study First Received: November 18, 2008
Last Updated: October 25, 2011
Health Authority: Argentina: Agencia Nacional de Medicamentos Alimentos y Tecnología

Additional relevant MeSH terms:
Diabetes Mellitus
Glucose Metabolism Disorders
Metabolic Diseases
Endocrine System Diseases
Aspirin
Atorvastatin
Anti-Inflammatory Agents, Non-Steroidal
Analgesics, Non-Narcotic
Analgesics
Sensory System Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Pharmacologic Actions
Anti-Inflammatory Agents
Therapeutic Uses
Antirheumatic Agents
Fibrinolytic Agents
Fibrin Modulating Agents
Molecular Mechanisms of Pharmacological Action
Cardiovascular Agents
Hematologic Agents
Platelet Aggregation Inhibitors
Cyclooxygenase Inhibitors
Enzyme Inhibitors
Antipyretics
Central Nervous System Agents
Anticholesteremic Agents
Hypolipidemic Agents
Antimetabolites
Lipid Regulating Agents

ClinicalTrials.gov processed this record on August 21, 2014